The AdultAIDS ClinicalTrials Group (AACTG) is a multicenter,multidisciplinary clinical trials group dedicated to the study of HIV pathogenesisand therapy. Since its inception in 1987, the AACTG has evolved into a cooperative group consisting of the Central Group (composed of the Office of the Group Chair, Executive, Scientific and Resource Committees, a state-of-the-art laboratory network, a Community ConstituencyGroup, and the OperationsCenter), 30 AIDS Clinical Trials Units (ACTUs) located at major academic medical centers, and the Statistical and Data Management Center. The AACTG has had a dramatic impact on elucidatingthe currentunderstanding of AIDS pathogenesisand therapy and has played a pivotal role in the developmentof novel trial designs and analysisstrategies. AACTG clinical trials have helped define guidelines for the use of antiretroviral agents and for the prophylaxis and treatment of HIV-associated opportunistic complications. Over 200 manuscripts have been published by the AACTG describing this body of work since submission of the prior competing renewal application in 1995. Group productivity has been greatly enhanced by collaborations with a wide variety of external investigators and laboratories, US and intemationalclinical trials networks, and the pharmaceutical and diagnostics industries. The Group proposes to build on these accomplishments with the goal of further reducing, and ultimately eliminating, HIV-associated morbidity and mortality. Investigationswill be undertaken in a structure that allows maximal efficiency and flexibility in the design and implementation of a broad array of clinicaltrials with patient management principlesreflectiveof contemporary clinical practice to insure maximal relevance of research findings. Over the next several years the Group proposes to address a number of issues including how best to: provide initial and subsequent treatment to maximally suppress HIV replication; provide optimum treatment strategies following reatment failure;develop approachesto individualizationof therapy based on genotypicand phenotypiccharacteristicsof the virus and/or lost; eliminate reservoirs of HIV-1 in latently infected cells; ameliorate virologic, immunologic, pharmacologic, and behavioral factors adherence) that contribute to treatment failure; incorporate new therapies and treatment strategies into future regimens; evaluate new strategiesfor enhancing immunereconstitutionto HIV and OIs; and delay or prevent HIV disease progression, opportunisticcomplications, complications of therapy, and mortality. To accomplish this agenda, the Group requests funding of 35 ACTUs based on objective performance criteria. New sites and laboratories have been added to provide additional critical expertise in virology, immunology,and pharmacology. The Group remainscommittedto enrollingwomen and minoritiesandto continuingsupport of the MinorityAIDSTraining Program. Appendices include the by-laws, SOPs, selected publications, international collaborations, and annual reports.